Microglia Activation in Asthma

Asthma Clinical Trial

— MAIA  

Official title:

Microglia Activation in Asthma

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04307667
• Other study ID #: 2019-1309
• Secondary ID: A483000L&S CTR F
• Status: Recruiting
• Start date: December 17, 2019
• Est. completion date: December 1, 2028

Study information

• Verified date: June 2023
• Source: University of Wisconsin, Madison
• Contact: Jane Sachs
• Phone: 6088902980
• Email: jfsachs[@]wisc.edu
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

The primary purpose of this study is to provide preliminary data to determine if an acute increase in airway inflammation, provoked by an inhaled allergen challenge, is associated with an increase in microglial activation and may inform whether individuals with asthma, in the long-term, are at increased risk for neurodegeneration, cognitive decline, and forms of dementia. Though in the long-term airway inflammation may be associated with neurodegenerative processes, these changes reflect the accumulation over a lifetime of allergen exposures and disease-related changes. This relationship between peripheral inflammation and microglial activation is analogous to the impact of sleep loss. No single night of poor sleep will lead to long-term change in brain structure, function, or cognitive function, but the accumulation of frequent and repeated sleep loss over a lifetime has been shown to have a major impact. These data will be used for a larger scale study to determine if asthma is a risk factor for neurodegeneration, and will inform brain health issues in asthma more broadly.

Description:

First schedule version:

Screening Visit 0: Consent/Eligibility, Pregnancy Test, Vital Signs, Medical History, Concomitant Meds, Allergy Skin Test, Spirometry, Physical Exam, Blood Draw, MRI Simulation, Fraction of exhaled nitric oxide (FeNO)

Screening Visit 0a: Pregnancy Test, Vital Signs, Adverse Events, Concomitant Meds, Spirometry, WLAC, Fraction of exhaled nitric oxide (FeNO)

Visit 1: Pregnancy Test, Vital Signs, Adverse Events, Concomitant Meds, Spirometry, Blood Draw, Sputum Induction, Fraction of exhaled nitric oxide (FeNO), Cognitive Tests, PET/MRI Scan, Questionnaires

Visit 2: Vital Signs, Adverse Events, Concomitant Meds, Spirometry, Physical Exam, WLAC, Blood Draw, Fraction of exhaled nitric oxide (FeNO)

Visit 3: Pregnancy Test, Vital Signs, Adverse Events, Concomitant Meds, Spirometry, Blood Draw, Sputum Induction, Fraction of exhaled nitric oxide (FeNO), Cognitive Tests, PET/MRI Scan, Questionnaires

Visit 4: Adverse Events, Spirometry, Fraction of exhaled nitric oxide (FeNO)

Second schedule version:

Screening Visit 0: Consent/Eligibility, Pregnancy Test, Vital Signs, Medical History, Concomitant Meds, Allergy Skin Test, Spirometry, Physical Exam, Blood Draw, MRI Simulation

Screening Visit 0a: Pregnancy Test, Vital Signs, Adverse Events, Concomitant Meds, Spirometry, WLAC

Visit 1: Pregnancy Test, Vital Signs, Adverse Events, Concomitant Meds, Spirometry, Blood Draw, Sputum Induction, Fraction of exhaled nitric oxide (FeNO), Cognitive Tests, PET/MRI Scan, Questionnaires

Visit 2: Vital Signs, Adverse Events, Concomitant Meds, Spirometry, Physical Exam, WLAC, Blood Draw, Fraction of exhaled nitric oxide (FeNO), Cognitive Tests, PET/MRI Scan, Questionnaires

Visit 3: Vital Signs, Adverse Events, Concomitant Meds, Spirometry, Blood Draw, Sputum Induction, Fraction of exhaled nitric oxide (FeNO)

Visit 4: Adverse Events, Spirometry, Fraction of exhaled nitric oxide (FeNO)

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 150
• Est. completion date: December 1, 2028
• Est. primary completion date: December 1, 2028
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 50 Years

Eligibility

Inclusion Criteria:

• Male or female with no health concerns that might affect the outcome of the study

• Physician diagnosis of asthma for at least six months prior to screening (can be determined at the discretion of an asthma/allergy physician member of the study team)

• At least a 20% decrease in forced expiratory volume (FEV1) during the immediate response following inhaled allergen challenge

• FEV1 > 70% at baseline

• Positive immediate skin test for allergies to ragweed, cat dander, or house dust mite (historical data documented within the last 5 years is acceptable)

• Women of child-bearing potential (WCBP) must have a negative urine pregnancy test for human chorionic gonadotropin (hCG) at screening and within 48 hours of the inhaled allergen challenge(s) and the positron emission tomography (PET) scans. WCBP must agree to use a medically-acceptable form of birth control for the duration of the study (medically-acceptable birth control methods can include: abstinence, barrier methods, oral contraceptives, injection contraceptives or skin absorption contraceptives).

• Asthma medications consisting of only inhaled beta-agonists taken as needed or leukotriene inhibitors

• Ability to tolerate a simulated functional magnetic resonance imaging (fMRI) brain scanning session

• In the opinion of the investigator, capable and willing to grant written informed consent and cooperate with study procedures and requirements

• High-affinity TSPO-binding genotype. Mixed (high/low) binding-affinity genotype may be included at principal investigator's (PI) discretion.

Exclusion Criteria:

• Current smoker (defined as more than 0.5 pack per week for the past 6 months and any smoking within two weeks of study procedures) or has a smoking history exceeding 5 pack years within the last 10 years

• Currently receiving immunotherapy

• Not able to withhold medication(s) as outlined by the study

• Use of psychotropic medication that might affect function of neurocircuitry implicated in the investigator's hypotheses at the discretion of the PI or Co-Investigator (Co-I)

• Needle phobia or claustrophobia

• Major health problems such as autoimmune disease, heart disease, uncontrolled hypertension or lung diseases other than asthma. The listed health problems are definitively exclusionary, but decisions regarding major health problems not listed will be based upon the judgment of the investigator.

• Pre-existing chronic infectious disease

• Use of inhaled corticosteroids or oral corticosteroids within 1 month of screening

• Use of an investigational drug within 30 days of entering the study. This criteria will be reviewed on a case by case basis by the principal investigators or co-investigator to determine appropriate washout period. Appropriate wash out period may be greater than 30 days depending on the half-life of the investigational drug. Participants may be eligible for study participation after completing the washout period designated by the PI or Co-I (physician only).

• Any MRI incompatibility as determined by WIMRs most current MRI screening form

• Does not fit in the MRI scanner

• History of a diagnosed Bipolar Disorder, Schizophrenia, or Schizoaffective Disorder

• History of serious head trauma or seizure disorder (can be included at the discretion of the PI or Co-I)

• Unable, in the judgement of the investigator, to comply with directions and/or tolerate the procedures required for participation in this study

• Pregnant or breast-feeding or has a planned pregnancy during the course of the study

• History of positive COVID-19 test (nasal swab or antibody test)

• Have corrected vision and are not able to wear contacts or see sufficiently well to read without glasses or contacts, as glasses will not fit in the PET/MR head coil

• Any other medical condition or disease that would impact subject safety or data integrity in the opinion of the PIs

Related Conditions & MeSH terms

• Asthma

Intervention

Biological:
• Whole lung antigen challenge (WLAC)
Whole lung antigen challenge with cat hair, house dust mite, short ragweed or cat hair allergen extracts.

Radiation:
• [18F]FEPPA
[18F]FEPPA is a radiotracer selective for translocator protein (TSPO) binding, which is elevated in activated microglia.

Locations

Country	Name	City	State
United States	University of Wisconsin Madison	Madison	Wisconsin

Sponsors (2)

Lead Sponsor	Collaborator
University of Wisconsin, Madison	National Heart, Lung, and Blood Institute (NHLBI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Functionality Measured by Statistical Significance of Co-variation between Cognitive Tasks or Self-Report Instruments and Microglial Activation	The investigators propose that a greater increase in microglial activation will be associated with reduced performance on tasks that assess cognitive function and greater psychological symptoms. The hypothesis is that a greater post-allergen challenge increase in microglial activation will be associated with a decrement in performance, relative to baseline, on measures of memory, attention, or executive function and elevated reports of depressive and anxious symptoms. The instruments may include the State-Trait Anxiety Inventory, Beck Depression Inventory, Beck Anxiety Inventory, Penn State Worry Questionnaire, Perceived Stress Scale, Stress and Adversity Inventory, Childhood Trauma and Adversity, and Peak Flow Diary (a diary of asthma symptoms recorded daily).	up to 10 days
Primary	Presence of Neuroinflammation measured by TSPO observed via PET scan	The investigators propose that, in subjects with asthma, provocation of airway inflammation activates microglia, indicative of a neuroinflammatory signal. The hypothesis is that microglial activation will occur following an inhaled allergen challenge, relative to pre-challenge. Activation of microglia will be measured using positron emission tomography (PET) with the radiotracer [18F]FEPPA, a tracer selective for translocator protein (TSPO) binding, which is elevated in activated microglia.	up to 9 days
Secondary	Intensity of Airway Response measured by Fraction of exhaled nitric oxide (FeNO) Level	The investigators propose that a more intense airway inflammatory response, created by the inhaled allergen challenge, will be associated with a greater increase in microglial activation. The hypothesis is that the increase in markers of airway inflammation, such as FeNO will be positively associated with the increase in microglial activation. Exhaled nitric oxide level will be determined using the Niox VERO instrumentation to measure FeNO. The test requires the participant to exhale into the mouthpiece of the FeNO measuring instrument for approximately 10 seconds.	up to 11 days
Secondary	Intensity of Airway Response measured by Sputum Eosinophil Count	The investigators propose that a more intense airway inflammatory response, created by the inhaled allergen challenge, will be associated with a greater increase in microglial activation. The hypothesis is that the increase in markers of airway inflammation, such as sputum eosinophil count will be positively associated with the increase in microglial activation. Sputum induction is a relatively simple, repeatable, and non-invasive method to collect airway secretions and are a highly relevant biological sample to assess airway inflammation.	up to 10 days